In Vivo Evaluation of Bone Regeneration by DNA/protamine Complex Treatment with Photothermal Stress Stimulation in an Aged Rat Calvarial Defect Model

SYNOPSIS DNA/protamine (D/P) complex was prepared and evaluated for new bone formation ability using a calvarial defect model in rats over 40 weeks old. Photothermal stress (42°C, 15 min) was repeated every day for up to 3 months to assess the effects of thermal stress on bone healing. Photothermal stress stimulation was carried out using a photothermal device, composed of an alginate gel containing carbon nanotubes and an irradiator supplying near-infrared light. Bone regeneration with the D/P complex was accelerated by photothermal stimulation compared with D/P complex implantation without thermal stimulation. There were no significant differences in Knoop hardness values between the newly formed bone, with or without photothermal stimulation, and peripheral bone. Microhardness measurement revealed that the regenerated bones were sufficiently mature. The results of this study suggested that photothermal stress stimulation upregulated bone regeneration induced by expression of heat shock-related